The advent of generic alternatives for transplant immunosuppressant drugs has engendered concern and discussion. The process by which the food and drug administration (FDA) approves generic substitutes is reviewed. A category of medicines deﬁned as narrow therapeutic index (NTI) drugs is deﬁned with evidence that many (but not all) of the commonly used transplant medications fall into this category. It is demonstrated that the current FDA standards are inadequate to vet NTI agents. Outcomes data are presented that show generic switching for NTI drugs can be successfully accomplished with careful blood level monitoring, but clinical and ﬁnancial negative consequences can ﬂow from unregulated switching. Recommendations are made for provider use of generic immunsuppressants, for recipient education and response to switching, and for pharmacy shandling of generic alternatives.